RealGiDo: A Real-World Study of Afatinib Dose Adjustment in patients with EGFR mutation-positive advanced NSCLC

RealGiDo: A Real-World Study of Afatinib Dose Adjustment in patients with EGFR mutation-positive advanced NSCLC

Afatinib Dose Adjustment in Clinical Practice

A global, multicenter medical chart review of first-line afatinib* dose adjustment in real-world clinical practice in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

Trial CT.gov-Identifier: NCT027518791

Watch the video below to find out more about the study design and outcomes of the RealGiDo study.

Patients2

  • Advanced, EGFR mutation-positive, tyrosine kinase inhibitor-naïve NSCLC
  • Common EGFR mutations (del19, L858R)
  • Treatment with afatinib according to the approved label
  • Patients who started treatment ≥6 months before enrollment

 

N=228

Analysis included patients treated with a reduced starting dose of afatinib (≤30 mg), those with a dose reduction (<40 mg) and those with no dose reduction (≥40 mg)

Outcome measures

 

Primary outcome measures:

  • Percentage of patients with adverse drug reactions (ADRs) by severity
  • Time to treatment failure (TTF; synonymous to time on treatment)
  • Time to progression (TTP)

Secondary outcome measure:

  • Percentage of patients receiving a modified starting dose, and reasons for modifying the starting dose

Results

Patients and Treatment

Baseline characteristics of patients in RealGiDo2 were generally consistent with the global, Phase III LUX-Lung 3 trial.3 However, in RealGiDo, there were more patients with EGFR Del19 mutations (78% vs 49%) and fewer Asian patients (44% vs 72%); furthermore, RealGiDo included patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 2–3 (12% of patients).2,3

Thirty-one percent of patients received a modified afatinib starting dose of <40 mg/day and the reasons for modifying the starting dose were broad but most commonly related to patient characteristics.2

Afatinib starting dose2

image

Reasons for modifying starting dose2

RealGiDo study: reasons for modified starting dose

EGFR TKI, epidermal growth factor receptor tyrosine kinase inhibitor.

Overall, 177 (78%) of patients in RealGiDo had a dose modification.2,4 Of these, 149 had dose reductions only, and 24 had both dose reductions and escalations.Among patients who received afatinib 40 mg/day as their starting dose, 86% of dose reductions occurred with the first 6 months of treatment and the rate of dose reductions was numerically higher in RealGiDo than LUX-Lung 3 (67% vs 53%).2,4

Safety

The overall safety profile of afatinib was similar in the overall population and in the group of patients who started with afatinib 40 mg/day.2 All-grade ADRs and Grade ≥3 ADRs occurred in 94% and 25% of the overall RealGiDo population, respectively.2 Among patients who received a starting dose of afatinib 40 mg/day (n = 155), 94% had an ADR, 28% had a Grade ≥3 ADR and 5% had a serious AE.2 There were fewer Grade ≥3 ADRs (28% vs 49%) and serious AEs (5% vs 14%) in patients treated with afatinib 40 mg/day in RealGiDo than in the LUX-Lung 3 trial.2,3

The most common ADRs in the overall population in RealGiDo were diarrhea, rash/acne, paronychia/nail effect and stomatitis/mucositis.2 The incidences of these ADRs were lower in RealGiDo than in LUX-Lung 3 (diarrhea, 75% vs 95%; rash/acne, 63% vs 89%; paronychia/nail effect, 49% vs 57%; stomatitis/mucositis, 34% vs 72%).2,3 Overall, no new safety signals were identified in RealGiDo.

Among the 91 patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day, 99% experienced an ADR of any grade prior to dose modification, compared with 71% after dose modification.2 The severity of ADRs was reduced following dose modification; the incidences of Grade 1, 2, 3 and 4 ADRs before and after dose modification were 11.0% and 20.6%, 57.5% and 37.0%, 27.4% and 12.3%, and 2.7% and 1.4%, respectively.2Dose reductions led to decreases in the incidence and severity of ADRs, including the most commonly reported.2

Among 71 patients who started on ≤30 mg/day afatinib, 95.8% had an ADR of any grade, 16.9% had a Grade 3 ADR and there were no Grade 4 ADRs.2

Overall safety profile before and after dose reduction in patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day2

RealGiDo study: Overall safety profile before and after dose reduction

Common ADRs before and after dose reduction in patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day4

RealGiDo study: Common ADRs before and after dose reduction

Overall safety profile by starting dose2

RealGiDo study: ADRs by starting dose

Effectiveness

TTF 

Median TTF was 18.7 months (95% confidence interval [CI]: 15.1–21.5) in the overall population, 19.5 months (95% CI: 13.4–not evaluable [NE]) in patients who remained on an afatinib dose of ≥40 mg/day for the first 6 months (n=66), 17.7 months (95% CI: 14.5–21.5) in patients who had a dose reduction to <40 mg/day within the first 6 months (n=91), and 19.4 months (95% CI: 12.9–NE) in patients who started with afatinib ≤30 mg/day (n=71; p=0.543).2

The proportion of patients remaining on treatment at 12 months was estimated as 70% in the patients who remained on ≥40 mg/day for the first 6 months, 74% in patients who had a dose reduction to <40 mg/day within the first 6 months and 66% in patients who started with afatinib ≤30 mg/day.2 The corresponding rates at 18 months were 53%, 50% and 53%, respectively.2

TTF among patients in RealGiDo by dose received2

RealGiDo study: TTF by dose received

CI, confidence interval; NR, no response.

TTP

Median TTP was 20.8 months (95% CI: 19.1–25.9) in the overall population, 29.0 months (95% CI: 17.9–NE) in patients who remained on an afatinib dose of ≥40 mg/day, 20.0 months (95% CI 14.7–23.0) in patients who had a dose reduction to <40 mg/day within the first 6 months and 25.9 months (95% CI: 17.3–NE) in patients who started with afatinib  ≤30 mg/day (p=0.392).2

The proportion of patients without progressive disease or tumor-related death at 12 months was estimated as 79% in patients who remained on afatinib ≥40 mg/day for the first 6 months, 84% in patients who had a dose reduction to <40 mg/day within the first 6 months and 86% in patients who started with afatinib ≤30 mg/day.2 The corresponding rates at 18 months were 65%, 60% and 64%, respectively.2

TTP among patients in RealGiDo by dose received2

RealGiDo study: TTP by dose received

CI, confidence interval; NR, no response.

Conclusion

Tolerability-guided afatinib dose adjustment in real-world clinical practice reduced the frequency and intensity of ADRs, without impacting effectiveness.2 As seen in the LUX-Lung trials,4,5 the effectiveness of afatinib was consistent regardless of whether patients had a dose reduction or a modified starting dose.2 Overall, these results show that outcomes can be supported by tailoring afatinib dose based on individual patient characteristics and ADRs.

Check full publication in the journal Lung Cancer.

References

1

Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02751879 (Accessed: September 2020).

2

Halmos B, et al. Lung Cancer 2019;127:103–11.

3

Sequist LV, et al. J Clin Oncol 2013;31(27):3327–34.

4

Yang JC, et al. Ann Oncol 2016;27(11):2103–10

5

Schuler M, et al. J Cancer Res Clin Oncol 2019;145(6):1569–79.

*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information.

 

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Last updated: January 2021